U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C22H26F3N3OS.2ClH
Molecular Weight 510.443
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of FLUPHENAZINE HYDROCHLORIDE

SMILES

Cl.Cl.OCCN1CCN(CCCN2C3=C(SC4=C2C=C(C=C4)C(F)(F)F)C=CC=C3)CC1

InChI

InChIKey=MBHNWCYEGXQEIT-UHFFFAOYSA-N
InChI=1S/C22H26F3N3OS.2ClH/c23-22(24,25)17-6-7-21-19(16-17)28(18-4-1-2-5-20(18)30-21)9-3-8-26-10-12-27(13-11-26)14-15-29;;/h1-2,4-7,16,29H,3,8-15H2;2*1H

HIDE SMILES / InChI

Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C22H26F3N3OS
Molecular Weight 437.522
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: Description was created based on several sources, including

Fluphenazine is a trifluoro-methyl phenothiazine derivative intended for the management of schizophrenia and other psychotic disorders. Fluphenazine has not been shown effective in the management of behaviorial complications in patients with mental retardation. Fluphenazine blocks postsynaptic mesolimbic dopaminergic D1 and D2 receptors in the brain; depresses the release of hypothalamic and hypophyseal hormones and is believed to depress the reticular activating system thus affecting basal metabolism, body temperature, wakefulness, vasomotor tone, and emesis.

Originator

Curator's Comment: Introduced in 1959

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
FLUPHENAZINE DECANOATE

Approved Use

Fluphenazine Decanoate Injection is a long­acting parenteral antipsychotic drug intended for use in the management of patients requiring prolonged parenteral neuroleptic therapy (e.g., chronic schizophrenics).

Launch Date

1987
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
2.3 ng/mL
12 mg single, oral
dose: 12 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FLUPHENAZINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
261 ng/mL
2.5 mg 3 times / 3 days multiple, intravenous
dose: 2.5 mg
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
FLUPHENAZINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
0.52 ng/mL
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FLUPHENAZINE plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
6.92 ng × h/mL
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FLUPHENAZINE plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
14.4 h
12 mg single, oral
dose: 12 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FLUPHENAZINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
12.3 h
2.5 mg 3 times / 3 days multiple, intravenous
dose: 2.5 mg
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
FLUPHENAZINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
13 h
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FLUPHENAZINE plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
0.6%
FLUPHENAZINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
21 mg 1 times / day multiple, intramuscular (max)
Recommended
Dose: 21 mg, 1 times / day
Route: intramuscular
Route: multiple
Dose: 21 mg, 1 times / day
Sources: Page: p.315
unhealthy, 35.4+/-10.4
n = 30
Health Status: unhealthy
Condition: Schizophrenia
Age Group: 35.4+/-10.4
Sex: M+F
Population Size: 30
Sources: Page: p.315
Disc. AE: Akathisia, Dyskinesia...
AEs leading to
discontinuation/dose reduction:
Akathisia (3.3%)
Dyskinesia (3.3%)
Hypertonia (3.3%)
Stupor (3.3%)
Sources: Page: p.315
250 mg 1 times / week multiple, intramuscular
Highest studied dose
Dose: 250 mg, 1 times / week
Route: intramuscular
Route: multiple
Dose: 250 mg, 1 times / week
Sources: Page: p.1438
unhealthy, 44
n = 25
Health Status: unhealthy
Condition: Schizophrenia
Age Group: 44
Sex: M+F
Population Size: 25
Sources: Page: p.1438
100 mg single, intramuscular|subcutaneous
Recommended
Dose: 100 mg
Route: intramuscular|subcutaneous
Route: single
Dose: 100 mg
Sources:
unhealthy
Disc. AE: Tardive dyskinesia, Neuroleptic malignant syndrome...
AEs leading to
discontinuation/dose reduction:
Tardive dyskinesia
Neuroleptic malignant syndrome
Fall
Sources:
AEs

AEs

AESignificanceDosePopulation
Akathisia 3.3%
Disc. AE
21 mg 1 times / day multiple, intramuscular (max)
Recommended
Dose: 21 mg, 1 times / day
Route: intramuscular
Route: multiple
Dose: 21 mg, 1 times / day
Sources: Page: p.315
unhealthy, 35.4+/-10.4
n = 30
Health Status: unhealthy
Condition: Schizophrenia
Age Group: 35.4+/-10.4
Sex: M+F
Population Size: 30
Sources: Page: p.315
Dyskinesia 3.3%
Disc. AE
21 mg 1 times / day multiple, intramuscular (max)
Recommended
Dose: 21 mg, 1 times / day
Route: intramuscular
Route: multiple
Dose: 21 mg, 1 times / day
Sources: Page: p.315
unhealthy, 35.4+/-10.4
n = 30
Health Status: unhealthy
Condition: Schizophrenia
Age Group: 35.4+/-10.4
Sex: M+F
Population Size: 30
Sources: Page: p.315
Hypertonia 3.3%
Disc. AE
21 mg 1 times / day multiple, intramuscular (max)
Recommended
Dose: 21 mg, 1 times / day
Route: intramuscular
Route: multiple
Dose: 21 mg, 1 times / day
Sources: Page: p.315
unhealthy, 35.4+/-10.4
n = 30
Health Status: unhealthy
Condition: Schizophrenia
Age Group: 35.4+/-10.4
Sex: M+F
Population Size: 30
Sources: Page: p.315
Stupor 3.3%
Disc. AE
21 mg 1 times / day multiple, intramuscular (max)
Recommended
Dose: 21 mg, 1 times / day
Route: intramuscular
Route: multiple
Dose: 21 mg, 1 times / day
Sources: Page: p.315
unhealthy, 35.4+/-10.4
n = 30
Health Status: unhealthy
Condition: Schizophrenia
Age Group: 35.4+/-10.4
Sex: M+F
Population Size: 30
Sources: Page: p.315
Fall Disc. AE
100 mg single, intramuscular|subcutaneous
Recommended
Dose: 100 mg
Route: intramuscular|subcutaneous
Route: single
Dose: 100 mg
Sources:
unhealthy
Neuroleptic malignant syndrome Disc. AE
100 mg single, intramuscular|subcutaneous
Recommended
Dose: 100 mg
Route: intramuscular|subcutaneous
Route: single
Dose: 100 mg
Sources:
unhealthy
Tardive dyskinesia Disc. AE
100 mg single, intramuscular|subcutaneous
Recommended
Dose: 100 mg
Route: intramuscular|subcutaneous
Route: single
Dose: 100 mg
Sources:
unhealthy
Overview

OverviewOther

Other InhibitorOther SubstrateOther Inducer


Drug as perpetrator​Drug as victimTox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Dystonic reactions to phenothiazine derivatives.
1966 Oct
Drug-induced extrapyramidal symptoms: their incidence and treatment.
1967 Jan
Treatment of resistant schizophrenics with extreme high dosage fluphenazine hydrochloride.
1970 Sep-Oct
Side effects of parenteral long-acting phenothiazines.
1972 Jan 22
The therapeutic use of diazepam for akathisia.
1973 Jul-Aug
Phenothiazine-induced decompensation.
1974 Jan
Antagonistic effect of cyproheptadine on neuroleptic-induced catalepsy.
1975 Jan-Feb
On the anticataleptic action of cyproheptadine.
1976 Aug
Schizophrenia-like reaction to diethylpropion.
1976 Nov 27
Phenothiazine-induced dystonic reaction while swimming.
1978 Oct 21
behavior of rats and mice administered active metabolites of fluphenazine, 7-hydroxy-fluphenazine and fluphenazine-sulfoxide.
1980 Nov
Fluphenazine pharmacokinetics and therapeutic response.
1981
Intrauterine effect of phenothiazines.
1981 Apr 18
Stuttering: an unusual side effect of phenothiazines.
1981 Mar
Neuroleptic-induced seizures. An in vitro technique for assessing relative risk.
1982 Feb
Sexual dysfunction in women using major tranquilizers.
1982 Sep
A case of neuroleptic malignant syndrome successfully treated with amantadine.
1982 Sep
[Malignant neuroleptics syndrome].
1984 Mar 9
A case of neuroleptic malignant syndrome in a mentally retarded adolescent.
1986 Nov
Effects of the 5-HT3 receptor antagonist, GR38032F, on raised dopaminergic activity in the mesolimbic system of the rat and marmoset brain.
1987 Dec
Propranolol withdrawal in psychosis.
1990 Apr
On the selection of mice for haloperidol response and non-response.
1991
Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D1.
1991 Apr 18
Nerve growth factor-stimulated calcium uptake into PC12 cells: uniqueness of the channel and evidence for phosphorylation.
1992 Apr
Interaction between fluoxetine and neuroleptics.
1993 May
Central effects of SL 82.0715, an antagonist of polyamine site of the NMDA receptor complex.
1993 Sep-Dec
The natural course of pseudotumor cerebri in lithium-treated patients.
1994 Aug
Relation of plasma fluphenazine levels to treatment response and extrapyramidal side effects in first-episode schizophrenic patients.
1994 Jan
Binding of typical and atypical antipsychotic agents to 5-hydroxytryptamine-6 and 5-hydroxytryptamine-7 receptors.
1994 Mar
Effects of concomitant risperidone and lithium treatment.
1995 Jul
Some behavioral effects of CNQX AND NBQX, AMPA receptor antagonists.
1995 Jul-Aug
Fluphenazine plasma levels, dosage, efficacy, and side effects.
1995 May
Some central effects of GYKI 52466, a non-competitive AMPA receptor antagonist.
1995 Nov-Dec
Differential effects of classical and newer antipsychotics on the hypermotility induced by two dose levels of D-amphetamine.
1995 Sep 5
Roxindole, a potential antidepressant. I. Effect on the dopamine system.
1996
Tardive dyskinesia induced by risperidone?
1996 Jun
The anticataleptic effect of 7-OH-DPAT: are dopamine D3 receptors involved?
1999
Case report of withdrawal syndrome after olanzapine discontinuation.
2000 Aug
H1-histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugs.
2003 Mar
Inhibition of cytochrome P450 enzymes participating in p-nitrophenol hydroxylation by drugs known as CYP2E1 inhibitors.
2004 Apr 15
Invited review: fluphenazine augments retinal oxidative stress.
2005 Aug
Stable expression of constitutively activated mutant h5HT6 and h5HT7 serotonin receptors: inverse agonist activity of antipsychotic drugs.
2005 May
Amphetamine improves cognitive function in medicated individuals with schizophrenia and in healthy volunteers.
2005 Sep 1
The neuroleptic drug, fluphenazine, blocks neuronal voltage-gated sodium channels.
2006 Aug 23
In silico prediction of pregnane X receptor activators by machine learning approaches.
2007 Jan
Relapse of tardive dyskinesia due to reduction in clozapine dose.
2009 Aug
An insight into the sialotranscriptome of the brown dog tick, Rhipicephalus sanguineus.
2010 Jul 22
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2.
2011 Jul 14
Antitubercular pharmacodynamics of phenothiazines.
2013 Apr
Phenothiazines inhibit hepatitis C virus entry, likely by increasing the fluidity of cholesterol-rich membranes.
2013 Jun
Patents

Sample Use Guides

In Vivo Use Guide
Curator's Comment: Fluphenazine Decanoate Injection may be given IM or SC
For most patients, a dose of 12.5 to 25 mg (0.5 to 1 mL) may be given to initiate therapy.
Route of Administration: Intramuscular
In Vitro Use Guide
30uM Fluphenazine inhibited the high-threshold Ca2 channel current in rat sympathetic neurons (blocking by 66%).
Substance Class Chemical
Created
by admin
on Fri Dec 15 17:20:58 GMT 2023
Edited
by admin
on Fri Dec 15 17:20:58 GMT 2023
Record UNII
ZOU145W1XL
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
FLUPHENAZINE HYDROCHLORIDE
JAN   MART.   ORANGE BOOK   USP   USP-RS   VANDF   WHO-DD   WHO-IP  
Common Name English
ANATENSOL
Common Name English
1-PIPERAZINEETHANOL, 4-(3-(2-(TRIFLUOROMETHYL)-10H-PHENOTHIAZIN-10-YL)PROPYL)-, DIHYDROCHLORIDE
Common Name English
FLUPHENAZINE HCL
Common Name English
FLUPHENAZINE HYDROCHLORIDE [VANDF]
Common Name English
FLUPHENAZINE HYDROCHLORIDE [USP IMPURITY]
Common Name English
SQUIBB 4918
Code English
FLUPHENAZINE DIHYDROCHLORIDE [MI]
Common Name English
DAPOTUM
Common Name English
FLUPHENAZINI HYDROCHLORIDUM [WHO-IP LATIN]
Common Name English
FLUPHENAZINE HYDROCHLORIDE [USP MONOGRAPH]
Common Name English
PERMITIL
Brand Name English
FLUPHENAZINE DIHYDROCHLORIDE
EP   MI  
Common Name English
NSC-179197
Code English
Fluphenazine hydrochloride [WHO-DD]
Common Name English
FLUPHENAZINE HYDROCHLORIDE [MART.]
Common Name English
FLUPHENAZINE HYDROCHLORIDE [JAN]
Common Name English
4-[3-[2-(Trifluoromethyl)phenothiazin-10-yl]propyl]-1-piperazineethanol dihydrochloride
Systematic Name English
FLUPHENAZINE HYDROCHLORIDE [USP-RS]
Common Name English
PROLIXIN
Brand Name English
FLUPHENAZINE HYDROCHLORIDE [WHO-IP]
Common Name English
FLUPHENAZINE HYDROCHLORIDE [ORANGE BOOK]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C29710
Created by admin on Fri Dec 15 17:20:58 GMT 2023 , Edited by admin on Fri Dec 15 17:20:58 GMT 2023
Code System Code Type Description
ECHA (EC/EINECS)
205-674-1
Created by admin on Fri Dec 15 17:20:58 GMT 2023 , Edited by admin on Fri Dec 15 17:20:58 GMT 2023
PRIMARY
EVMPD
SUB02232MIG
Created by admin on Fri Dec 15 17:20:58 GMT 2023 , Edited by admin on Fri Dec 15 17:20:58 GMT 2023
PRIMARY
DRUG BANK
DBSALT000288
Created by admin on Fri Dec 15 17:20:58 GMT 2023 , Edited by admin on Fri Dec 15 17:20:58 GMT 2023
PRIMARY
NSC
179197
Created by admin on Fri Dec 15 17:20:58 GMT 2023 , Edited by admin on Fri Dec 15 17:20:58 GMT 2023
PRIMARY
PUBCHEM
67356
Created by admin on Fri Dec 15 17:20:58 GMT 2023 , Edited by admin on Fri Dec 15 17:20:58 GMT 2023
PRIMARY
RS_ITEM_NUM
1282004
Created by admin on Fri Dec 15 17:20:58 GMT 2023 , Edited by admin on Fri Dec 15 17:20:58 GMT 2023
PRIMARY
MERCK INDEX
m5490
Created by admin on Fri Dec 15 17:20:58 GMT 2023 , Edited by admin on Fri Dec 15 17:20:58 GMT 2023
PRIMARY Merck Index
NCI_THESAURUS
C47995
Created by admin on Fri Dec 15 17:20:58 GMT 2023 , Edited by admin on Fri Dec 15 17:20:58 GMT 2023
PRIMARY
CAS
146-56-5
Created by admin on Fri Dec 15 17:20:58 GMT 2023 , Edited by admin on Fri Dec 15 17:20:58 GMT 2023
PRIMARY
DAILYMED
ZOU145W1XL
Created by admin on Fri Dec 15 17:20:58 GMT 2023 , Edited by admin on Fri Dec 15 17:20:58 GMT 2023
PRIMARY
ChEMBL
CHEMBL726
Created by admin on Fri Dec 15 17:20:58 GMT 2023 , Edited by admin on Fri Dec 15 17:20:58 GMT 2023
PRIMARY
EPA CompTox
DTXSID00892922
Created by admin on Fri Dec 15 17:20:58 GMT 2023 , Edited by admin on Fri Dec 15 17:20:58 GMT 2023
PRIMARY
WHO INTERNATIONAL PHARMACOPEIA
FLUPHENAZINE HYDROCHLORIDE
Created by admin on Fri Dec 15 17:20:58 GMT 2023 , Edited by admin on Fri Dec 15 17:20:58 GMT 2023
PRIMARY Description: A white or almost white, crystalline powder; odourless. Solubility: Soluble in 10 parts of water; sparingly soluble in ethanol (~750 g/l) TS; practically insoluble in ether R. Category: Neuroleptic.Storage: Fluphenazine hydrochloride should be kept in a well-closed container, protected from light. Additional information: Even in the absence of light, Fluphenazine hydrochloride is gradually degraded on exposure to a humid atmosphere, the decomposition being faster at higher temperatures. Definition: Fluphenazine hydrochloride contains not less than 98.5% and not more than 101.5% of C22H26F3N3OS,2HCl, calculated with reference to the dried substance.
FDA UNII
ZOU145W1XL
Created by admin on Fri Dec 15 17:20:58 GMT 2023 , Edited by admin on Fri Dec 15 17:20:58 GMT 2023
PRIMARY
RXCUI
203207
Created by admin on Fri Dec 15 17:20:58 GMT 2023 , Edited by admin on Fri Dec 15 17:20:58 GMT 2023
PRIMARY RxNorm
SMS_ID
100000090436
Created by admin on Fri Dec 15 17:20:58 GMT 2023 , Edited by admin on Fri Dec 15 17:20:58 GMT 2023
PRIMARY
Related Record Type Details
BASIS OF STRENGTH->SUBSTANCE
ASSAY (HPLC)
USP
PARENT -> SALT/SOLVATE
BASIS OF STRENGTH->SUBSTANCE
ASSAY (TITRATION)
EP
Related Record Type Details
IMPURITY -> PARENT
at 260 nm
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
UNSPECIFIED
EP
IMPURITY -> PARENT
274 nm
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
at 260 nm
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
IMPURITY -> PARENT
274 nm
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
UNSPECIFIED
EP
IMPURITY -> PARENT
Related Record Type Details
ACTIVE MOIETY